This invention relates to a pharmaceutical composition which is readily reconstitutable in water. In particular, this invention relates to a composition which contains galacticol as carrier for a therapeutic agent such as cyclophosphamide.
Cyclophosphamide is a widely used synthetic antineoplastic drug and immunosuppressive agent for the treatment of a variety of malignant and non-malignant diseases. It exists in two forms: anhydrous and monohydrate. The monohydrate form is employed in processing for clinical applications because the anhydrous form is not stable. At comparatively low relative humidity, the monohydrate will lose the water of hydration.
Cyclophosphamide has been made into unit dosage compositions by mixing the dry powder with sodium chloride to provide isotonicity when the product is reconstituted. The disadvantages of the dry powder blend include formation of mixtures of powders which are not pharmaceutically elegant, i.e., not of uniform appearance and/or consistency, contaminated with insoluble particulates, and having prolonged dissolution time when reconstituting into a solution.
The disadvantages of dry powder formulations have been addressed by lyophilizing an aqueous solution of the formulated material, to obtain a solid composition of improved stability. The advantages of lyophilization are (1) the solution of the drug can be filtered to remove particulates, and (2) the time required for reconstitution is significantly reduced. The lyophilized product also appears to be more stable to heat.
One patent which specifically addresses the lyophilization of cyclophosphamide is U.S. Pat. No. 4,537,883 issued Aug. 27, 1985. The formulation of this patent includes cyclophosphamide with mannitol as excipient and a range of moisture content of 1.25 to 2 parts by weight of water. The composition is shown to have improved physical stability over the dry formulation. It also shows enhanced appearance over the dry formulation and over lyophilizates incorporating lactose and other excipients.
It is an object of the present invention to identify another excipient which would yield a physically and chemically stable lyophilizate as an alternative to mannitol, and to identify a carrier for lyophilized pharmaceutical compositions which allows for faster reconstitution in water than mannitol. Surprisingly, of the other excipients besides mannitol, only galactitol exhibits the physical and chemical stability necessary for a feasible commercial product.